Intra-arterial Chemotherapy Combined with Radiotherapy and Immunotherapy for HNSCC

NCT06725498 | Recruiting Phase 2

• 1 other identifier: TREC2023-KY073
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study pioneers a novel approach by integrating a new auxiliary chemo-immunotherapy regimen, which is then followed by an evaluation of the potential for surgical resection. For those patients who remain non-resectable, a tailored treatment plan is proposed, consisting of arterial infusion chemotherapy in conjunction with radiotherapy, succeeded by a series of immune checkpoint inhibitors. The efficacy and safety of this integrated therapeutic strategy are meticulously assessed, with the goal of enhancing survival outcomes for patients with T4bNanyM0 HNSCC.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 1 year Event-free Survival rate (1y-EFS rate)

  EFS is the time from the starting date of neoadjuvant therapy to the date of first record of any of the following events: radiographic disease progression; local or distant progression or recurrence as assessed with imaging or biopsy as indicated; or death due to any cause. Radiographic disease progression during neoadjuvant phase that precludes surgery will be considered an event; a secondary malignancy will not be considered an event.

  1 year

Secondary Outcomes (7)

• Objective Response Rate (ORR)

  Up to 30 days post-neoadjuvant

• Pathological Complete Response (pCR)

  Up to 30 days post-surgery

• Major Pathological Response (MPR)

  Up to 30 days post-surgery

• Overall Survival (OS)

  Up to 5 years

• Percentage of Participants Experiencing An Adverse Event (AEs)

  through study completion, an average of 2 years

Study Arms (1)

RT + IAC + Anti-PD-1 antibody

EXPERIMENTAL

Patients must undergo Multi-Disciplinary Treatment evaluation after receiving 3 cycles of neoadjuvant therapy (Tislelizumab-jsgr combined with platinum-based chemotherapy). For operable patients, Radical surgery followed by adjuvant standard (chemo)radiotherapy plus Tislelizumab-jsgr (Q3W 17 cycles). For inoperable patients, Intra-arterial Chemotherapy concurrent with Radical radiotherapy followed by Tislelizumab-jsgr (Q3W 17 cycles).

Drug: Tislelizumab-jsgr; Drug: Cisplatin; Drug: Albumin-Bound Paclitaxel; Radiation: Radiotherapy

Interventions

Tislelizumab-jsgr DRUG

200mg, Q3W

RT + IAC + Anti-PD-1 antibody

Cisplatin DRUG

60-75 mg/㎡, Q3W

RT + IAC + Anti-PD-1 antibody

Albumin-Bound Paclitaxel DRUG

260 mg/㎡, Q3W

RT + IAC + Anti-PD-1 antibody

Radiotherapy RADIATION

Radical Radiotherapy or adjuvant Radiotherapy per guidelines.

RT + IAC + Anti-PD-1 antibody

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with T4bNanyM0 Head and neck squamous cell carcinoma (hypopharyngeal cancer, laryngeal cancer, oropharyngeal cancer or oral cavity) with a confirmed diagnosis by histology and/or cytology;
• Expected survival ≥3 months, with adequate organ function;
• Investigators believe they can safely receive treatment with PD-1 combined with platinum and albumin-bound paclitaxel;
• Age ≥18 years;
• ECOG score of 0-1;
• Measurable disease as defined by RECIST v1.1;
• Adequate bone marrow reserve and organ function: Absolute neutrophil count (ANC) ≥1,000/microliter (mcL), platelets ≥75,000/mcL, hemoglobin ≥8g/dL, without transfusion or dependence on erythropoietin (EPO) (within 7 days after assessment);
• Renal function: Serum creatinine ≤1.5 times the upper limit of normal (ULN) OR measured or calculated creatinine clearance ≥60mL/min with creatinine levels \> 1.5 times the institutional ULN. (GFR can also be used in place of creatinine or CrCl). Creatinine clearance should be calculated according to institutional standards;
• Liver function: For subjects with a total bilirubin level \>1.5 ULN, serum total bilirubin ≤1.5 times ULN or direct bilirubin ≤ULN; For patients with liver metastases, aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤2.5 times ULN OR ≤5 times ULN; Albumin \> 2.5 mg/dL;
• Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN, if the subject is receiving anticoagulant therapy, PT or PTT should be within the permissible range of the anticoagulant used;
• Females should agree to use contraceptive measures (such as intrauterine device (IUD), oral contraceptives, or condoms) during the study and for 6 months after the study ends; Negative serum or urine pregnancy test within 7 days before study entry, and must be non-lactating patients; Males should agree to use contraceptive measures during the study and for 6 months after the study ends.

You may not qualify if:

• Patients with a history of prior immunotherapy, radiotherapy, and treatment with EGFR monoclonal antibodies;
• Patients with a history of other (including unknown primary) malignant tumors within the past 5 years;
• Patients who are intolerant to radiotherapy post-surgery;
• Patients known to be allergic to the study medication or its active ingredients, excipients;
• Patients with any unstable systemic diseases, including but not limited to: severe infections, uncontrolled diabetes, unstable angina, cerebrovascular accidents or transient ischemic attacks, myocardial infarction, congestive heart failure, serious arrhythmias requiring medication, liver, kidney, or metabolic disorders;
• Patients with potential immune deficiencies, chronic infections, including HIV, hepatitis, tuberculosis (TB), or autoimmune diseases;
• Patients with potential hematological issues, including bleeding disorders, known prior gastrointestinal bleeding requiring intervention within the past 6 months, active pulmonary embolism or deep vein thrombosis (DVT) that is unstable on anticoagulation regimens;
• A history or any evidence of active noninfectious pneumonia;
• Known active central nervous system (CNS) metastases and/or leptomeningeal disease or carcinomatous meningitis. Subjects with previously treated brain metastases may participate if they are stable (no evidence of imaging progression for at least four weeks prior to the first trial treatment and any neurological symptoms have returned to baseline), with no new or enlarging evidence of brain metastases, and are not on steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability;
• Concurrent use (or receipt) of medications within 7 days prior to Day 1 of Cycle 1 that may affect drug metabolism;
• Pregnant or breastfeeding, or expecting to become pregnant or father a child during the anticipated trial period;
• Any uncontrollable concomitant diseases, including but not limited to persistent or active infections, symptomatic congestive heart failure, unstable angina, arrhythmias;
• Prolonged corrected QT (QTc) interval \> 475 ms on screening EKG;
• Ejection fraction \<40% on 2D echocardiogram (ECHO) at screening;
• Any serious medical or psychiatric illness/condition, including substance use disorders, that may interfere with or limit adherence to study requirements/treatment in the investigator's judgment;

Sponsors & Collaborators

• Beijing Tongren Hospital: lead

Study Sites (1)

Beijing Tongren Hospital Affiliated to Capital Medical University

Beijing, Beijing Municipality, 10000, China

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cisplatin; Albumin-Bound Paclitaxel; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Therapeutics

Central Study Contacts

Xiaohong Chen, Dr.

CONTACT

+86-10-58266699; trchxh@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2024
• First Posted: December 10, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2029
• Last Updated: December 10, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)